Rational Pharmacotherapy in Children: Challenges of Off-Label Use and Drug Safety

The field of pediatric clinical pharmacology faces persistent challenges in balancing therapeutic innovation with safety, particularly when treating conditions for which age-appropriate formulations or clinical data are limited. Off-label drug use in children remains both widespread and necessary, reflecting the historical underrepresentation of pediatric populations in clinical trials. Although such practices can be essential for providing timely treatment, they raise significant concerns regarding variations in dosing, drug formulation, efficacy extrapolation from adults, and long-term safety. Recent large-scale pharmacoepidemiologic analyses and multicentre studies have shown that off-label prescribing in pediatrics can reach rates of 30–70% depending on the drug class and setting, underlining the continued gap between regulatory approval and clinical necessity. These findings underscore the importance of developing a robust evidence base and improved governance frameworks to enhance rational pharmacotherapy in children.

This Research Topic aims to close critical evidence gaps by bringing together multidisciplinary perspectives on pediatric off-label drug use and safety. It will examine the pharmacological, clinical, ethical, and regulatory dimensions that shape current prescribing patterns and safety outcomes. Contributors are encouraged to address key questions such as: What are the predictors and risk profiles of off-label medication use in children? How can pharmacovigilance systems and real-world data improve safety monitoring? What strategies can optimize benefit–risk assessment, evidence generation, and policy alignment across different healthcare systems? By aggregating research across clinical, regulatory, and methodological domains, this topic seeks to promote standardized and safer drug use practices tailored to pediatric physiology and population needs.

This Research Topic will consider contributions spanning clinical evidence, policy analysis, and pharmacoepidemiologic evaluation. The scope is broad but focused on rational pharmacotherapy in children and adolescents, with a preference for work that bridges real-world evidence and clinical applicability. To gather further insights into the evolving landscape of pediatric drug use, we welcome submissions addressing, but not limited to, the following themes:

o Epidemiology of pediatric off-label and unlicensed drug use in different healthcare settings

o Advances in pediatric drug safety monitoring and pharmacovigilance approaches

o Clinical pharmacokinetics and dose optimization in off-label contexts

o Risk–benefit evaluation and evidence translation for pediatric therapies

o Global and national regulatory frameworks and policy harmonization

o Ethical considerations and informed consent practices in pediatric drug use

o Digital health tools and real-world data applications for pediatric safety evaluation

o Development, evaluation and management of pediatric-specific formulations

o Implementation, interventions and optimization of pediatric medication guidelines

Article types: Original Research, Systematic Reviews, Mini Reviews, Brief Research Reports, Case Reports, Case Series, and Perspective or Policy articles.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Pediatric Pharmacotherapy, Off-Label Drug Use, Pediatric Drug Safety, Pharmacovigilance, Dose Optimisation, Pediatric Formulations, Regulatory Policy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.